当前位置： SCI文献检索 > NEUROPHARMACOLOGY期刊下所有文献 > Repeated treatment with alpidem, a new anxiolytic, does not induce tolerance or physical dependence.

Repeated treatment with alpidem, a new anxiolytic, does not induce tolerance or physical dependence.

Abstract：

:Alpidem is a new anxiolytic of imidazopyridine structure which has a high affinity for the omega 1 (BZ1) modulatory site of the GABAA receptor. The present study investigated whether tolerance and physical dependence develop after repeated treatment with alpidem, as is observed with benzodiazepines. Mice were given alpidem (100 mg/kg, p.o.) or diazepam (5 mg/kg, p.o.) twice daily for 10 consecutive days. Tolerance was assessed by measuring antagonism of pentylenetetrazole- and isoniazid-induced convulsions and bicuculline-provoked mortality, following repeated drug treatment. Decreases in the latency to isoniazid-induced convulsions and in the minimal convulsant dose of pentylenetetrazole were taken as an index of physical dependence and were evaluated at different times (3, 6, 14, 42, 67, 96 hr) after drug withdrawal or after flumazenil administration. In addition, changes in sensitivity to the convulsant effect of a beta-carboline (beta-CCM) were measured. Repeated treatment with diazepam produced tolerance to its anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3-5. After discontinuation of diazepam treatment, spontaneous withdrawal occurred within 24 hr and lasted 67 hr as indicated by decreases in the threshold for convulsions induced by isoniazid and pentylenetetrazole. Flumazenil-induced withdrawal was observed in both isoniazid and pentylenetetrazole-induced convulsion models. Hypersensitivity of mice to the convulsant effect of beta-CCM also occurred. In contrast, repeated treatment with alpidem did not produce tolerance to its anticonvulsant effects and neither spontaneous nor flumazenil-induced withdrawal was observed in the pentylenetetrazole and isoniazid models. Moreover, withdrawal of alpidem did not induce any change in the convulsant activity of beta-CCM. These differences between alpidem and diazepam may be related to the low level of receptor occupancy during repeated treatment with alpidem because of its selectivity for omega 1 (BZ1) sites and to its moderate intrinsic activity.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Perrault G,Morel E,Sanger DJ,Zivkovic B

doi

10.1016/0028-3908(93)90140-x

subject

Has Abstract

pub_date

1993-09-01 00:00:00

pages

855-63

issue

9

eissn

0028-3908

issn

1873-7064

journal_volume

32

pub_type

杂志文章

相关文献

NEUROPHARMACOLOGY文献大全
  • Interactions between CAP70 and actinfilin are important for integrity of actin cytoskeleton structures in neurons.

    abstract：:The integrity of dynamic actin structures is coupled to a variety of neurological processes. Actin-binding proteins play a critical role in regulating actin structure dynamics. A link between actin-binding proteins and receptor interacting scaffolding proteins may provide a conduit for transmitting signaling events to...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2005.05.022

    authors： Chen Y,Li M

    更新日期：2005-12-01 00:00:00

  • NMDA receptor-dependent function and plasticity in inhibitory circuits.

    abstract：:NMDA receptors have been known to play a central role in long-term potentiation at glutamatergic synapses in principal cells for thirty years. In contrast, their roles in the development and activity-dependent plasticity of synapses in inhibitory circuits have only recently begun to be understood. Progress has, to a g...

    journal_title：Neuropharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.neuropharm.2013.03.004

    authors： Moreau AW,Kullmann DM

    更新日期：2013-11-01 00:00:00

  • The influence of G protein subtype on agonist action at D2 dopamine receptors.

    abstract：:In previous studies, we have shown that agonists influence the ability of D2 dopamine receptors to couple to G proteins and here we extend this work. The human D2Short dopamine receptor and a natural polymorphism of this D(2Short)(Ser311Cys), have been studied by co-expressing the receptors in insect cells with Gbeta1...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2004.06.010

    authors： Nickolls SA,Strange PG

    更新日期：2004-11-01 00:00:00

  • Activation of mGluRII induces LTD via activation of protein kinase A and protein kinase C in the dentate gyrus of the hippocampus in vitro.

    abstract：:The involvement of metabotropic glutamate receptor group II (mGluRII) in the induction of long-term depression (LTD) was investigated in the medial perforant path of the rat dentate gyrus, a region with a very high density of mGluRII. Perfusion of either of two potent mGluRII agonists, (2S,1R,2R,3R)-2-(2S, 1'R, 2'R, 3...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/s0028-3908(98)00168-3

    authors： Huang L,Killbride J,Rowan MJ,Anwyl R

    更新日期：1999-01-01 00:00:00

  • Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others.

    abstract：:Cholecystokinin (CCK) is the most abundant neuropeptide in the central nervous system. In the hippocampal CA1 region, CCK is co-localized with GABA in a subset of interneurons that synapse on pyramidal cell somata and apical dendrites. CCK-containing interneurons also uniquely express a high level of the cannabinoid r...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2007.06.023

    authors： Karson MA,Whittington KC,Alger BE

    更新日期：2008-01-01 00:00:00

  • In vitro and in vivo effect of BU99006 (5-isothiocyanato-2-benzofuranyl-2-imidazoline) on I2 binding in relation to MAO: evidence for two distinct I2 binding sites.

    abstract：:BU99006 is an irreversible I(2) ligand which selectively inactivates I(2) binding sites, making it an ideal tool with which to study I(2) site mechanism. We sought to determine the effects of BU99006 on I(2) binding in relation to monoamine oxidase (MAO), and the time course of these effects. In vitro, rat brain membr...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2006.08.010

    authors： Paterson LM,Tyacke RJ,Robinson ES,Nutt DJ,Hudson AL

    更新日期：2007-02-01 00:00:00

  • Novel compounds selectively enhance delta subunit containing GABA A receptors and increase tonic currents in thalamus.

    abstract：:Inhibition in the brain is dominated by the neurotransmitter gamma-aminobutyric acid (GABA); operating through GABA(A) receptors. This form of neural inhibition was presumed to be mediated by synaptic receptors, however recent evidence has highlighted a previously unappreciated role for extrasynaptic GABA(A) receptors...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2008.08.004

    authors： Wafford KA,van Niel MB,Ma QP,Horridge E,Herd MB,Peden DR,Belelli D,Lambert JJ

    更新日期：2009-01-01 00:00:00

  • Pharmacological studies on a new benzamide derivative, YM-09151-2, with potential neuroleptic properties.

    abstract：:The electrophysiological properties and cataleptogenicity of YM-09151-2 (N-[(2RS, 3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-methylaminobenzamide) were studied in the cat. This drug inhibited the EEG arousal response to electrical stimulation of the mesencephalic reticular formation with the same pote...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(82)90105-8

    authors： Yamamoto M,Usuda S,Tachikawa S,Maeno H

    更新日期：1982-10-01 00:00:00

  • Salvinorin A exerts opposite presynaptic controls on neurotransmitter exocytosis from mouse brain nerve terminals.

    abstract：:We investigated the effects of salvinorin A on the basal and the 12 mM K(+)-evoked release of preloaded [(3)H]noradenaline ([(3)H]NA) and [(3)H]serotonin ([(3)H]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12mM K(+)-evoked release of preloaded [(3)H]dopamine ([(3)H]DA) from ...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2009.07.023

    authors： Grilli M,Neri E,Zappettini S,Massa F,Bisio A,Romussi G,Marchi M,Pittaluga A

    更新日期：2009-10-01 00:00:00

  • High affinity, heterogeneous displacement of [3H]EBOB binding to cerebellar GABA A receptors by neurosteroids and GABA agonists.

    abstract：:Heterogeneous binding interactions of cerebellar GABA(A) receptors were investigated with GABA agonists and neurosteroids. GABA(A) receptors of rat cerebellum were labelled with [(3)H]ethynylbicycloorthobenzoate (EBOB), a convulsant radioligand. Saturation analysis revealed a homogenous, nanomolar population of [(3)H]...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2005.04.003

    authors： Maksay G,Bíró T

    更新日期：2005-09-01 00:00:00

  • The effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test: anxiolysis vs. pain modulation.

    abstract：:The aim of the present study was to evaluate, by means of quantitative and multivariate analyses, the effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test as well as whether such changes are associated with drug-induced effects on anxiety and/or nociception. To this purpo...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2012.03.026

    authors： Casarrubea M,Sorbera F,Santangelo A,Crescimanno G

    更新日期：2012-08-01 00:00:00

  • Impaired inhibition of epileptiform activity by baclofen, but not by adenosine in the weaver hippocampus.

    abstract：:The weaver defect results in a loss of baclofen- and adenosine-gated K+ conductance in the hippocampus of adult homozygous (wv/wv) mice. In addition, suppression of hippocampal epileptiform activity by baclofen is impaired (Jarolimek, W., Bäurle, J., Misgeld, U., 1998. Pore mutation in a G protein-gated inwardly recti...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/s0028-3908(99)00089-1

    authors： Jarolimek W,Bäurle J,Misgeld U

    更新日期：2000-01-04 00:00:00

  • In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: role of 5-HT1A receptors.

    abstract：:The ventral part of the medial prefrontal cortex (mPFC) plays an important role in mood and cognition. This study examined the effect of the 5-HT in this region by measuring the electrophysiological response of ventral mPFC neurones to electrical stimulation of the dorsal and median raphe nuclei (DRN and MRN), which a...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/s0028-3908(03)00139-4

    authors： Hajós M,Gartside SE,Varga V,Sharp T

    更新日期：2003-07-01 00:00:00

  • Effect of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidin) cyclohexyl]-benzeneacetamide (U-50,488H), a kappa opioid receptor agonist, on intake of food in food-deprived and non-deprived spontaneously hypertensive and normotensive Wistar-Kyoto rats.

    abstract：:The effect of U-50,488H, a selective kappa opioid receptor agonist on the intake of food in food-deprived and non-deprived spontaneously hypertensive and normotensive Wistar-Kyoto rats was determined. In food deprived Wistar-Kyoto rats, intraperitoneal administration of U-50,488H, produced a bell-shaped curve on the i...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(89)90069-5

    authors： Bhargava HN,Ramarao P,Richter CM,Bieniarz AA

    更新日期：1989-01-01 00:00:00

  • BGC20-761, a novel tryptamine analog, enhances memory consolidation and reverses scopolamine-induced memory deficit in social and visuospatial memory tasks through a 5-HT6 receptor-mediated mechanism.

    abstract：:Inhibition of 5-HT(6) receptors has been shown to improve memory consolidation, thus we tested whether a novel tryptamine analog with high affinity for 5-HT(6) receptors, BGC20-761 (5-methoxy-2-phenyl-N,N-dimethyltryptamine, PMDT), can enhance long-term memory. BGC20-761 (10 mg/kg i.p.) alone had no effect on social r...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2005.10.002

    authors： Mitchell ES,Hoplight BJ,Lear SP,Neumaier JF

    更新日期：2006-03-01 00:00:00

  • Activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) reverses referred mechanical hyperalgesia induced by colonic inflammation in mice.

    abstract：:In the current study, we investigated the effect of the activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) on dextran sulphate sodium (DSS)-induced colitis and referred mechanical hyperalgesia in mice. Colitis was induced in CD1 male mice through the intake of 4% DSS in tap water for 7 days. Control...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2012.06.004

    authors： Costa R,Motta EM,Manjavachi MN,Cola M,Calixto JB

    更新日期：2012-10-01 00:00:00

  • Depression-related behavior and mechanical allodynia are blocked by 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene in a mouse model of neuropathic pain induced by partial sciatic nerve ligation.

    abstract：:Clinically, it is suggested that chronic pain might induce mood disorders like depression and anxiety. Based on this antidepressant drugs have emerged as a new therapy for pain. In this study, the effect of acute and subchronic treatments with 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene (F-DPS) on behavioral cha...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2014.01.020

    authors： Gai BM,Bortolatto CF,Brüning CA,Zborowski VA,Stein AL,Zeni G,Nogueira CW

    更新日期：2014-04-01 00:00:00

  • Spinal superfusion of dopamine excites renal sympathetic nerve activity.

    abstract：:Chloralose-anesthetized rats, spinalized at C1, were used to investigate the effects of spinal infusion of dopamine on renal sympathetic nerve activity (RSNA). A subarachnoid spinal superfusion technique was used to localize dopamine in the spinal cord while renal sympathetic nerve activity was recorded from the left ...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(83)90242-3

    authors： Simon OR,Schramm LP

    更新日期：1983-03-01 00:00:00

  • Therapeutic strategies to target acute and long-term sequelae of pediatric traumatic brain injury.

    abstract：:Pediatric traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality in children. Experimental and clinical studies demonstrate that the developmental age, the type of injury (diffuse vs. focal) and sex may play important roles in the response of the developing brain to a traumatic injur...

    journal_title：Neuropharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.neuropharm.2018.06.025

    authors： Huh JW,Raghupathi R

    更新日期：2019-02-01 00:00:00

  • The actions of (-)N-n-propylnorapomorphine and selective dopamine D1 and D2 receptor agonists to modify the release of [3H]dopamine from the rat nucleus accumbens.

    abstract：:The ability of (-)N-n-propylnorapomorphine and selective D1 and D2 dopamine receptor agonists and antagonists to modify the release of [3H]dopamine, induced by potassium from the nucleus accumbens, was studied using an in vitro superfusion technique. (-)N-n-Propylnorapomorphine, in picomolar concentrations, inhibited ...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(90)90090-e

    authors： Barnes JM,Barnes NM,Costall B,Naylor RJ

    更新日期：1990-04-01 00:00:00

  • Selective GABA(A) α5 positive allosteric modulators improve cognitive function in aged rats with memory impairment.

    abstract：:A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer's disease. Compounds that act as positive allosteric modulators at GABA(A) α5 receptors might be useful in targeting this condition because GABA(A) α5 rece...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2012.06.023

    authors： Koh MT,Rosenzweig-Lipson S,Gallagher M

    更新日期：2013-01-01 00:00:00

  • Differential regulation of microglial P2X4 and P2X7 ATP receptors following LPS-induced activation.

    abstract：:Activation of microglia has been implicated in many neurological conditions including Alzheimer's disease and neuropathic pain. Recent studies provide evidence that P2X ATP receptors on the surface of microglia play a crucial role in initiation of inflammatory cascades. We investigated changes in surface P2X receptors...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2007.06.010

    authors： Raouf R,Chabot-Doré AJ,Ase AR,Blais D,Séguéla P

    更新日期：2007-09-01 00:00:00

  • Induction of Fos proteins in regions of the nucleus accumbens and ventrolateral striatum correlates with catalepsy and stereotypic behaviours induced by morphine.

    abstract：:A history of intermittent exposures to drugs of abuse can cause long-term changes in acute behavioural responses to a subsequent drug exposure. In drug-naive rats, morphine can elicit intermittent cataleptic postures followed by sustained increases in locomotor activity. Chronic intermittent morphine treatment can red...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2009.01.003

    authors： Hamlin AS,McNally GP,Westbrook RF,Osborne PB

    更新日期：2009-03-01 00:00:00

  • Safinamide inhibits in vivo glutamate release in a rat model of Parkinson's disease.

    abstract：:To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were administered to 6-hydroxydopamine hemilesioned rats, a model of...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2020.108006

    authors： Pisanò CA,Brugnoli A,Novello S,Caccia C,Keywood C,Melloni E,Vailati S,Padoani G,Morari M

    更新日期：2020-05-01 00:00:00

  • Morphine decreases cerebral glucose utilization in limbic and forebrain regions while pain has no effect.

    abstract：:Morphine alters affective states in humans and produces reinforcement in humans and animal subjects. Therefore, the present study was designed to determine whether morphine affected the functional activity in brain structures involved in emotion and motivation. Since opioid-induced analgesia largely reflects an influe...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(91)90195-h

    authors： Cohen SR,Kimes AS,London ED

    更新日期：1991-02-01 00:00:00

  • Genetics of attention-deficit hyperactivity disorder (ADHD).

    abstract：:Attention-deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous syndrome which is comorbid with childhood conduct disorder, alcoholism, substance abuse, dis-social personality disorder, and affective disorders. A small but consistent overlap with autistic symptoms has also been establishe...

    journal_title：Neuropharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.neuropharm.2009.08.011

    authors： Sharp SI,McQuillin A,Gurling HM

    更新日期：2009-12-01 00:00:00

  • The dopaminergic system modulates the endogenous opioid system in guinea-pig isolated ileal longitudinal muscle.

    abstract：:The effects of the dopamine antagonists haloperidol and sultopride were investigated on the twitch response, evoked by 0.1 Hz stimulation of guinea-pig isolated ileal longitudinal muscle, and on the inhibition of the twitch response induced by 10 Hz stimulation (post-tetanic twitch inhibition) and by application of op...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(94)00166-p

    authors： Ozaki M,Miyamoto Y,Kishioka S,Masuda Y,Yamamoto H

    更新日期：1995-05-01 00:00:00

  • Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist--a review of preclinical data.

    abstract：:N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential in numerous CNS disorders ranging from acute neurodegeneration (e.g. stroke and trauma), chronic neurodegeneration (e.g. Parkinson's disease, Alzheimer's disease, Huntington's disease, ALS) to symptomatic treatment (e.g. epilepsy, Parkinson's ...

    journal_title：Neuropharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/s0028-3908(99)00019-2

    authors： Parsons CG,Danysz W,Quack G

    更新日期：1999-06-01 00:00:00

  • Venlafaxine exhibits pre-clinical antidepressant activity in the resident-intruder social interaction paradigm.

    abstract：:Venlafaxine, a novel 2-phenyl-2-(1-hydroxycycloalkyl) ethylamine, is a potent inhibitor of 5-hydroxytryptamine and noradrenaline reuptake and exhibits a profile of activity in pre-clinical in vitro biochemical studies predictive of antidepressant activity. The studies described here examined the effects of acute and c...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/0028-3908(93)90065-b

    authors： Mitchell PJ,Fletcher A

    更新日期：1993-10-01 00:00:00

  • P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone.

    abstract：:Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular...

    journal_title：Neuropharmacology

    pub_type： 杂志文章

    doi：10.1016/j.neuropharm.2013.05.017

    authors： Messemer N,Kunert C,Grohmann M,Sobottka H,Nieber K,Zimmermann H,Franke H,Nörenberg W,Straub I,Schaefer M,Riedel T,Illes P,Rubini P

    更新日期：2013-10-01 00:00:00